Project description:BackgroundSuccessful management of gestational diabetes mellitus (GDM) reduces the risk of morbidity in women and newborns. A woman's blood glucose readings and risk factors are used by clinical staff to make decisions regarding the initiation of pharmacological treatment in women with GDM. Mobile health (mHealth) solutions allow the real-time follow-up of women with GDM and allow timely treatment and management. Machine learning offers the opportunity to quickly analyze large quantities of data to automatically flag women at risk of requiring pharmacological treatment.ObjectiveThe aim of this study is to assess whether data collected through an mHealth system can be analyzed to automatically evaluate the switch to pharmacological treatment from diet-based management of GDM.MethodsWe collected data from 3029 patients to design a machine learning model that can identify when a woman with GDM needs to switch to medications (insulin or metformin) by analyzing the data related to blood glucose and other risk factors.ResultsThrough the analysis of 411,785 blood glucose readings, we designed a machine learning model that can predict the timing of initiation of pharmacological treatment. After 100 experimental repetitions, we obtained an average area under the receiver operating characteristic curve of 0.80 (SD 0.02) and an algorithm that allows the flexibility of setting the operating point rather than relying on a static heuristic method, which is currently used in clinical practice.ConclusionsUsing real-time data collected via an mHealth system may further improve the timeliness of the intervention and potentially improve patient care. Further real-time clinical testing will enable the validation of our algorithm using real-world data.
Project description:BackgroundNon-pharmacological interventions are the first line of Gestational diabetes mellitus (GDM) management. Community-based interventions are cheaper, more accessible, with higher patient satisfaction.ObjectivesTo systematically review community-based non-pharmacological interventions and evaluate their effectiveness for GDM.Search strategyTwelve bibliographic databases and reference list of related studies from inception until January 2022.Selection criteriaAll primary studies of community-based non-pharmacological interventions for GDM reported in English which investigated any behavioural or clinical outcome(s).Data collection and analysisData were extracted using modified Cochrane's data extraction template. Studies were evaluated using Cochrane Collaboration's risk of bias tool. Narrative synthesis was used to summarise findings. This study is registered with PROSPERO (CRD42021257634).Main resultsTwenty-seven studies involving 6,242 pregnant women with GDM investigated self-management programmes, medical nutrition/diet therapy, exercise/physical activity, combined diet and exercise, calcium plus vitamin D supplementation, and continuous glucose monitoring. Self-management programmes were more effective than routine care in improving self-efficacy, two-hour postprandial blood glucose, and lifestyle behaviours but were as effective as routine care in improving infant birth weight. Self-management programmes were superior to or as effective as usual care in improving fasting blood glucose, blood glucose control, glycated haemoglobin, macrosomia, and preterm delivery. Medical nutrition/diet therapy was more effective than usual care in improving postprandial blood glucose levels. Postprandial blood glucose levels were better improved by regular supervised exercise plus daily brisk walks or a daily walking intervention than routine obstetric care or no treatment. The effects of exercise/physical activity programmes were mostly inconsistent for other outcomes. Diet and exercise were superior to diet alone in reducing maternal weight gain although there were similar outcomes for other pregnancy and foetal outcomes. Limited or conflicting evidence was found for other outcomes and interventions including calcium and vitamin D supplementation and continuous glucose monitoring intervention.ConclusionsCommunity-based non-pharmacological interventions are more effective than placebo; and are more or as effective as usual care. Self-management programmes and medical nutrition/diet therapy had the most promising GDM outcomes.FundingThere was no funding for this study. The study design, data collection, data analysis and interpretation, and writing of this manuscript were not influenced externally by any funder.
Project description:Background/objectiveThe prevalence of diabetic ketoacidosis (DKA) in gestational diabetes mellitus (GDM) is very low. We describe a patient with GDM in whom severe DKA with intrauterine fetal demise developed in the setting of nonadherence to therapy.Case reportA 33-year-old woman, G2P0010, with no preexisting diabetes mellitus (DM) presented at 30 weeks of gestation with acute-onset altered sensorium, nausea, and emesis. GDM was diagnosed at 15 weeks of gestation with a serum glucose level of 266 mg/dL (70-134 mg/dL) after 1-hour 50-gram glucose challenge test. Glycated hemoglobin (HbA1C) was 5.9% (41 mmol/mol) at the time of GMD diagnosis. Insulin was initiated at week 20 of gestation. On presentation, serum glucose level of 920 mg/dL (70-110 mg/dL), pH of 7.02 (7.32-7.43), anion gap level of 38 mmol (5-17 mmol), bicarbonate level of 5.0 mEq/L (22-29 mEq/L), and large serum ketones were found. Ultrasound showed intrauterine fetal demise. She received intravenous fluids and continuous insulin. Following the spontaneous delivery of a nonviable fetus, DKA was resolved. Negative antiglutamic acid decarboxylase, islet cell, and zinc transporter 8 antibodies, C-peptide level of 2.4 ng/dL (1.1-4.4 ng/dL), and HbA1C level of 9% (75 mmol/mol) were found. Inpatient management included basal-bolus and sliding scale insulin therapies. Metformin was added upon discharge 7 days after admission. The HbA1C levels were 5.3% (34 mmol/mol) and 5% (31 mmol/mol) at the 3- and 6-month follow-ups, respectively. Insulin was discontinued. Currently, the patient is on metformin and glucagon-like peptide 1 receptor agonist.DiscussionThe development of insulin resistance during pregnancy is driven by multiple factors. Approximately 1% to 2% of pregnant women with impaired glucose tolerance develop DKA; most cases occur in women with type 1 DM. The approximate incidence of DKA in GDM is 0.02%.ConclusionDKA complicating GDM is extremely infrequent, but it cannot be dismissed. Early recognition along with prompt and appropriate medical and obstetrical management is critical.
Project description:Now, no recommendations of gestational weight gain (GWG) after gestational diabetes mellitus (GDM) diagnosis for Chinese women was made. This study aimed to explore the optimal GWG after oral glucose tolerance test (OGTT) for Chinese women with GDM. The GWG status of 11,570 women was retrospectively analyzed. Binary regression model and restricted cubic spline were used to estimate the association between GWG after OGTT and the predicted probability of adverse outcomes. Based on above, the optimal GWG was defined as the range that not exceed 1% increase in the predicted probability from the lowest point. Results shown that every increased one unit GWG after OGTT was associated with higher risks of macrosomia, cesarean section and LGA, and lower risk of preterm birth. According to the WHO and Working Group on Obesity in China (WGOC) recommended pre-pregnancy BMI category, the optimal GWG were proposed: 3.66 to 6.66 kg/3.66 to 6.66 kg in underweight group, 3.07 to 6.50 kg/3.02 to 6.40 kg in normal weight group, 1.06 to 2.73 kg/0 to 1.99 kg in overweight group, and not applicable/- 0.22 to 2.53 kg in obese group, respectively. Therefore, it is necessary to classified Chinese population based on the WGOC recommended pre-pregnancy BMI category, that influenced the contribution of pre-pregnancy BMI groups and the optimal GWG recommendation for GDM women with overweight or obesity.
Project description:Objectives Studies that use continuous glucose monitoring (CGM) to monitor women with gestational diabetes (GDM), highlight the importance of managing dysglycemia over a 24-hour period. However, the effect of current treatment methods on dysglycemia over 24-hrs are currently unknown. This study aimed to characterise CGM metrics over 24-hrs in women with GDM and the moderating effect of treatment strategy. Methods Retrospective analysis of CGM data from 128 women with GDM in antenatal diabetes clinics. CGM was measured for 7-days between 30-32 weeks gestation. Non-parametric tests were used to evaluate differences of CGM between periods of day (morning, afternoon, evening, and overnight) and between treatment methods (i.e., diet alone or diet+metformin). Exploratory analysis in a subgroup of 34 of participants was performed to investigate the association between self-reported macronutrient intake and glycaemic control. Results Glucose levels significantly differed during the day (i.e., morning to evening; P<0.001) and were significantly higher (i.e., mean blood glucose and area under the curve [AUC]) and more variable (i.e., SD and CV) than overnight glucose levels. Morning showed the highest amount of variability (CV; 8.4% vs 6.5%, P<0.001 and SD; 0.49 mmol/L vs 0.38 mmol/L, P<0.001). When comparing treatment methods, mean glucose (6.09 vs 5.65 mmol/L; P<0.001) and AUC (8760.8 vs 8115.1 mmol/L.hr; P<0.001) were significantly higher in diet+metformin compared to diet alone. Finally, the exploratory analysis revealed a favourable association between higher protein intake (+1SD or +92 kcal/day) and lower mean glucose (-0.91 mmol/L p, P=0.02) and total AUC (1209.6 mmol/L.h, P=0.021). Conclusions Glycemia varies considerably across a day, with morning glycemia demonstrating greatest variability. Additionally, our work supports that individuals assigned to diet+metformin have greater difficulty managing glycemia and results suggest that increased dietary protein may assist with management of dysglycemia. Future work is needed to investigate the benefit of increased protein intake on management of dysglycemia.
Project description:The diagnosis of gestational diabetes is usually very stressful for pregnant women, especially because they fear that insulin treatment may become necessary. Knowledge about personal risk factors predicting the probability of insulin treatment could therefore help to improve acceptance of the diagnosis and therapy adherence. The aim of this study was to find potential risk factors for insulin dependency and treatment requirements using information available at the time of diagnosis of gestational diabetes during pregnancy. We included 454 singleton pregnancies diagnosed ≥24 weeks of gestation. Multivariate regression analysis was used to evaluate independent associations of metabolic, anthropometric and fetal ultrasound parameters with the general need for insulin treatment and further stratified treatment options: diet (n = 275), bolus insulin only (n = 45), basal insulin only (n = 73) and multiple daily injections (n = 61). Receiver operator characteristics and cut-off values for independent variables were generated. Treatment groups differed significantly concerning pre-pregnancy weight and BMI as well as fasting glucose and 1 h glucose test values. Significant cut-offs for insulin dependency were HbA1c level of 5.4%, FPG of 5.5 mmol/L and 1 h glucose of 10.6 mmol/L. At time of diagnosis, certain patient characteristics and measurements can help to predict treatment necessities and therefore improve individualized counselling.
Project description:In this study, transcriptome sequencing was conducted on placentas obtained from both normal pregnancies and pregnancies with GDM to investigate the molecular mechanisms underlying this condition. Placental tissue samples were immersed in ice-cold phosphate-buffered saline (PBS) to remove blood contamination. Sections with a thickness of 4 µm were cut from the block and stained with Hematoxylin and eosin (HE) staining. The resulting slides were examined and photographed under a light microscope (Olympus).The original sequencing data were subjected to sequencing analysis, resulting in the identification of 935 upregulated genes and 256 downregulated genes. The Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analysis techniques on differential genes uncovered evidence suggesting that the phosphoinositide 3-kinase (PI3K) /Akt signaling pathway may contribute to the pathogenesis of GDM. Subsequent analysis indicated that the expression levels of MMP11, MMP12, MMP14, and MMP15, which are regulated by the PI3K/Akt pathway, were upregulated in the placentas of patients with GDM when compared to those of individuals with normal placental function. Additionally, our investigation into alternative splicing patterns revealed an increase in exon skipping alternative splicing of CSF3R in the placenta of patients with GDM compared to that in the control group.
Project description:Oral semaglutide (Rybelsus®) is a glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1RA) with 94% homology to human GLP-1. It is the first GLP-1RA developed for oral administration, and it comprises a co-formulation of the peptide semaglutide with the absorption enhancer sodium N-(8-[2-hydroxybenzoyl] amino) caprylate, which overcomes the challenges of peptide absorption in the acidic conditions of the stomach. Oral semaglutide is indicated for use as an add-on combination therapy (with other glucose-lowering agents, including insulin) or as a monotherapy (in patients who are intolerant to metformin) for type 2 diabetes when diet and exercise do not provide adequate glycemic control. In an extensive phase III clinical program including patients from across the disease spectrum, treatment with oral semaglutide resulted in effective glycemic control, reductions in body weight, and decreases in systolic blood pressure when used as monotherapy or in combination with other glucose-lowering therapies. Studies showed that oral semaglutide was well tolerated, with a safety profile consistent with the GLP-1RA drug class. The risk of hypoglycemia was low, and the most common adverse events were gastrointestinal, with nausea and diarrhea generally being the most frequently reported manifestations. Cardiovascular (CV) safety was shown to be noninferior to placebo and observations suggest that the CV profile of oral semaglutide is likely to be similar to that of subcutaneous semaglutide. The evolution of the GLP-1RA class to include an oral agent could facilitate the use of these agents earlier in the diabetes treatment cascade owing to wider acceptance from patients and healthcare professionals.